One-Pot N-Arylation of Indoles Directly from N-Arylsulfonylindoles via Consecutive Deprotection and SNAr Reactions with Activated Aryl Halides

Abstract

An efficient one-pot step by step t-BuOK-mediated procedure for the synthesis of N-arylindoles has been developed in moderate to good yields. The protocol involves the consecutive deprotection of N-arylsulfonylindoles as latent indoles and subsequent SNAr reactions with activated aryl halides. This tandem reaction affords an efficient and convenient preparation of N-arylindoles that benefit from prior indoles protection by arylsulfonyl group, and can shorten a reaction sequence and improve synthetic efficiency.

Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen Synthase Kinase-3β Inhibitors

“…A modification of the protocol described by Xu et al using a high excess of K t BuO (7 eq.) instead of refluxing conditions allowed a fast deprotection at room temperature [33]. This approach gave intermediates 12a – d in satisfying purity and yields (64–77% over three steps), justifying the synthetic detour associated with the protection of the indole nitrogen.…”

Antifungal Agents. Part 3: Synthesis and Antifungal Activities of 3‐Acylindole Analogs against Phytopathogenic Fungi In Vitro

“…3‐Acylindole analogs ( 8 – 20 ) (12): A mixture of 3‐acyl‐ N ‐( p ‐toluenesulfonyl)indoles (1 mmol) and t ‐BuOK (1.8 mmol) in anhydrous tetrahydrofurame (THF) (5 mL) was stirred at reflux under argon. The progress of the reaction was monitored by TLC analysis.…”

“…Twenty 3-acylindole analogs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were screened in vitro for their antifungal activities against seven phytopathogenic fungi by poisoned food technique (8). Seven phytopathogenic fungi, namely Fusarium graminearum, Alternaria alternata, Bipolaris sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp.…”

“…Indoles were firstly protected with p-toluenesulfonyl chloride in the presence of sodium hydroxide (NaOH) and TEBA at room temperature to give N-(p-toluenesulfonyl)indoles in 92-96% yields. Subsequently, treatment of N-(p-toluenesulfonyl)indoles with acetic anhydride, propionic anhydride or n-hexanoyl chloride by a regioselective Friedel-Crafts acylation reaction followed by indole deprotection led to 3-acylindole analogs (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in 40-73% yields, which were well characterized by 1 H NMR, EI-MS, and mp.…”

Synthesis of Differentially Protected Azatryptophan Analogs via Pd2(dba)3/XPhos Catalyzed Negishi Coupling of N-Ts Azaindole Halides with Zinc Derivative from Fmoc-Protected tert-Butyl (R)-2-Amino-3-iodopropanoate

“…While it was relatively straightforward to identify deprotection conditions to selectively remove the Fmoc and t Bu moieties, identifying the right conditions for selective N -Ts deprotection proved to be considerably more challenging. The majority of the known reaction conditions − for N -Ts deprotection led to deprotection of either the Fmoc or t Bu under basic or acidic conditions, respectively. , After numerous attempts, selective deprotection of N -Ts group on the 7-azatryptophan 3c was achieved by using a 0.1 M solution of SmI 2 in THF in the presence of pyrrolidine which furnished 4 in 78% isolated yield. The applications of the selectively deprotected Negishi products were further demonstrated in the synthesis of dipeptides at both C- and N-terminals.…”